LRP5 p.Ser60=
c.180C>T · rs533073394 · VCV1652012
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00666%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -2.5 |
| Overall | ||
| CADD | 2.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
African / African-American · 5/75,052 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.00273%
44/1,613,894 alleles · very rare
exomes 41/1,461,552 · genomes 3/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00666% | 15,010 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| European (non-Finnish) | 0.00305% | 32,779 |
| East Asian | 0.00223% | 44,886 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- LRP5
- Protein
- p.Ser60=
- Coding
- c.180C>T
- MANE Select
- NM_002335
- dbSNP
- rs533073394
- Type
- single nucleotide variant
- Location
- chr11:68347935 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.94 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.65
- Residue 60
- the 'beta-propeller 1' region
Similar variants
- LRP5 p.Ser60Arg Uncertain significance ★ same residue
- LRP5 c.1412+1G>A Pathogenic ★★ same type
- LRP5 c.2827+1G>A Pathogenic ★★ same type
- LRP5 c.3236+2T>G Pathogenic/Likely pathogenic ★★ same type
- LRP5 c.4488+2T>G Pathogenic/Likely pathogenic ★★ same type
- LRP5 c.884-2A>G Likely pathogenic ★★ same type
- LRP5 p.Ala214Thr Pathogenic ★★ same type
- LRP5 p.Ala242Thr Pathogenic/Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lrp5-p-ser60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown